Superfetation: Pregnant while already pregnant

Some weeks back, I came across a case report published in 1999 in the journalUltrasound in Obstetrics and Gynecology . It presented a twin pregnancy wherein one of the fetuses seemed to be at a younger developmental stage in its mother’s womb compared to its sibling.

It wasn’t the first time that I had stumbled on a report which detailed a discordance in the growth of a fetus in a twin pregnancy. In fact, cases of growth discordance in multiple pregnancies are not uncommon and may be due to a number of problems such as the placenta’s inability to adequately support the development of more than one fetus, twin-to-twin transfusion syndrome whereby blood is disproportionately transferred from one twin to the other, or other disorders which may as easily occur in single pregnancies (congenital infection, aneuploidy, etc). However, the 1999 case report observed that the twin pregnancy was uneventful and resulted in the delivery of live healthy babies. It concluded that a phenomenon known as superfetation had occurred.

Superfetation is the onset of a subsequent pregnancy during an ongoing pregnancy; a new pregnancy during an initial pregnancy. It happens when there is fertilization of an ovule by a sperm cell while a conceptus is already present in the womb. Intriguing, isn’t it? I thought so and dug deeper in the literature to realize that superfetation had actually been extensively reported in animals .

The phenomenon of superfetation in animals has long been speculated as far back as fourth century B.C by Aristotle. Aristotle came to this thought when he observed that hares often gave birth to litters which comprised sets of healthy and imperfect offsprings. He deduced that the imperfect offsprings were younger ones who had spent less time in their mother’s womb—a direct consequence of superfetation. In effect, Aristotle was supposing that the younger offsprings were from a litter which was the result of the second pregnancy.

The badger, American mink, panther, buffalo and swamp wallaby are a few examples of mammals in which superfetation is well documented. Last year, a paper published in Nature Communications reported that superfetation frequently occurred in the European brown hare, even postulating that it may actually be an evolutionary adaptation . For this reason, it is probable that many more mammals may be accustomed to superfetation.

While there is evidence that superfetation may indeed be part of the reproductive processes of certain animals, in humans, it is in all likelihood a rare reproductive abnormality . In other words, it probably occurs by accident. Because for superfetation to occur, a number of things must happen—things that a woman’s reproductive cycle is intrinsically programmed to prevent.

First, for any pregnancy to occur, an ovule must be present. And for an ovule to be present, ovulation must have taken place. Therefore, for superfetation to be possible, ovulation must be triggered during an ongoing pregnancy. And this is a major stumbling block right there. While ovulation happens every month in a fertile woman, it is normally impeded during pregnancy. During the early stages of pregnancy, this is due to the corpus luteum, the surrounding tissue from which the ovule is shed during ovulation. It remains for a couple of days and releases hormones which ultimately prevent further ovulation. If implantation of a conceptus then occurs, the corpus luteum stays for longer still, actively secreting more hormones. Eventually this endocrine role is taken over by the placenta. Therefore, strictly speaking, ovulation can only occur when neither the corpus luteum nor the placenta is present.

Pregnancy also requires the fertilization of the ovule with a sperm cell. This means that semen from the male must be able to attain the ovule in the female’s oviduct. When a woman is pregnant however, a mucus plug is formed in the cervix, blocking the passage of sperm. This mechanism prevents semen from passing through the pregnant uterus, let alone allowing it to reach the oviduct. The mechanism is an important measure against microbes contained in semen which can cause venereal diseases to the fetus. It also prevents the possibility of superfetation.

Finally, a viable pregnancy also requires proper implantation to occur. And for superfetation to occur, the conceptus needs to implant in a pregnant uterus. Implantation is only possible in a delicate and specific environment controlled by different hormones though. Under normal conditions, the appropriate uterine environment is catered for in a woman who is ovulating rather than in one who is pregnant. In addition, space is also an issue in the crowded already-occupied uterus!

In order for superfetation to occur in humans, therefore, it would appear that three seemingly impossible things need to happen: ovulation must take place during an ongoing pregnancy, semen must somehow find its way through the blocked cervix to the oviduct, via the occupied uterus and finally, the conceptus has to successfully implant itself in an unsuspecting already-occupied uterus. The odds of all three of them happening are without doubt extremely small as reflected by the very occasional reports of superfetation in humans in the medical literature.

It should not be surprising then, that reports of superfetation in humans are more commonly associated with women who have undergone fertility treatments. At least this is what I found when during my digging. A case report published in 2005 in the The Journal of Pediatrics, for instance, describe how a 32-year-old woman who had undergone embryo transfer later became pregnant with twins and one additional growth-discordant fetus . Initially, two out of the three embryos transferred to the woman’s uterus implanted themselves and a viable twin pregnancy was pronounced. The third embryo did not develop into a fetus. However, a triple pregnancy was discovered around five months later, when a third smaller fetus was seen by ultrasound. This fetus was deduced to be around three weeks younger than its siblings. This led to the conclusion that there had been a subsequent fertilization and implantation following the successful double implantation from artificial insemination.

During fertility treatments, it is hoped that a woman’s reproductive cycle will come to terms with events that it normally would not have to go through. Taking the above case to illustrate, three embryos were artificially transferred into the woman’s uterus. The norm however, is one ovule per cycle and thus one embryo for implantation—not three! But when the human body is faced with the unusual aspects of pregnancy brought about by artificial reproductive technologies, some mechanisms are more prone to go astray. For example, it is documented that a normal ovulatory response can result in following cycles of controlled ovarian hyperstimulation even if an early pregnancy is present.

Hacking Memory to Break Drug Addiction

Using a chemical that blocks the creation of memories, scientists have prevented rats from using cocaine after they had become addicted to the drug. The hope is that doctors will one day be able to give humans some version of the chemical and stop cocaine addiction in its tracks.

Barry Everitt, an experimental psychologist at the University of Cambridge in England, focused his group's efforts on proteins calledNMDA-type glutamate receptors in rat brains. Previous work on addiction and post-traumatic stress has shown that these proteins—which are found on the surface of brain cells—are essential to memory formation. The receptors are also crucial to reconsolidating a memory—moving it from its storage area in long-term memory to brain regions that handle short-term memory.

The researchers—who report their findings in the Journal of Neuroscience—put rats in a cage with a lever in it for a couple of hours per day for a week. When the animalspushed the lever, a light would come on and a cocaine solution would be dispensed to the rat. The rats began to associate the light they saw with cocaine.

After a couple weeks of forced sobriety, the animals were returned to the cage. Before going back in, some of the rats received injections of experimental drugs that block NMDA-type glutamate receptors in the amygdala—a brain region that has been implicated in drug-associated memories.

Both treated and untreated animals, when back in the cage, would press the lever over and over again. The light would come on, but no cocaine would be served. Untreated animals continued unfazed, hoping cocaine would eventually come out.

For the treated animals, however, Everitt says, "They press the lever, but it doesn't do anything, so they stop." The animals seemed to forget that the light in the cage meant cocaine was on its way for up to four weeks after only a single treatment.

Scientists say that suggests that by disrupting the recollection of a drug-associated memory—a person one abuses drugs with, a place that one uses drugs at, for example—a therapeutic may be able to break the connection between cues in the environment and the need for drugs. Sometimes these cues can be quite close to home—a family member or loved one.

Yavin Shaham, a neurobiologist at the National Institute on Drug Abuse in Bethesda, Md., said in a press statement that the new work is an example of "basic research that can be readily translated to the treatment of cocaine addiction in humans."

With no approved medications on the market to specifically treat cocaine addiction, most treatment regimens rely of behavioral therapy. Often, according to Everitt, these therapies involve exposing addicts to cues that they associate with drug use—but in the absence of the illicit substance. Once a recovered addict encounters these cues back in the real world though, they often relapse. Everitt suggests using an NMDA-type glutamate receptor blocker in the clinic could improve that treatment.

Karim Nader, a behavioral neuroscientist at McGill University in Montreal, called the new research "promising" for treating addiction, adding that he doesn't know of a one-time treatment that causes rodents to stop taking drugs for long periods of time.

Everitt notes that while the drugs used in the current study are experimental, there are several drugs approved by the U.S. Food and Drug Administration that target the same receptors: Dextramethorphan, which is found in many over-the-counter cough suppressants and memantine, a drug approved to slow the progression of Alzheimer'sdisease, are examples.

Mouse Study Suggests Why Addictions Are Hard to Forget

A new study finds that alcoholic mice more readily form Pavlovian associations with addictive substances. Similar subconscious memories may haunt recovering addicts


Recovering addicts are often told to avoid the people, places, and things connected with their addiction—tried-and-true advice that may be gaining support from neuroscience. A view widely accepted among addiction researchers is that drug abuse can cause the brain to form persistent, enduring associations between a drug and the environment in which it is purchased and consumed. These mental ties represent a subconscious form of learning and contribute to the tenacious grip of addictions.

"There's a growing consensus in the addiction field that addiction is a learning and memory disorder. We learn behavior associated with these drugs too well." saysHitoshi Morikawa, a neurobiologist at the University of Texas at Austin. New research from Morikawa's lab, published April 6 in the Journal of Neuroscience, found that repeated use of alcohol can make the brain more susceptible to forming reward-based associations. Mice given a weeklong binge of alcohol were more likely to remember the environment in which they later received cocaine. In human addicts similar associations could explain why certain environments are apt to trigger relapse.

Pavlovian memories
Addictive drugs cause dopamine neurons, which synthesize and store the neurotransmitter dopamine, to release it, signaling to other brain areas to take note of the context surrounding the drug—the better to replicate the experience in the future. "We can think of those neurons that release dopamine as 'teachers' that tell other brain areas, the 'students,' to learn the associations surrounding rewards such as food, sex and addictive drugs," Morikawa explains. In essence, alcohol and other addictive drugs help the "teachers" teach better.

Morikawa emphasizes that the study does not show that alcohol improves "conscious" forms of learning and memory—a fact that could be corroborated by many a college freshman. Indeed, alcohol use is known to cause both acute and lasting damage to cognitive function.

The type of learning that alcohol and other addictive drugs may promote is best described as "subconscious" reward-based conditioning, much like the classic example of Pavlov's dog. Just as the dog learns to associate the sound of a bell with food (a reward), a person may similarly associate a particular street corner in his hometown with cocaine use. After much repetition the dog salivates at the sound of a bell, and a cocaine addict craves a hit when he returns to the old hangout. The new insight from Morikawa's work is that alcoholics may be more vulnerable to reward-based conditioning—meaning they would learn new cravings sooner.

Earlier work by Morikawa's lab, also on mice, showed that repeated amphetamine use has a similar positive effect on reward-based conditioning. Morikawa expects likewise from other addictive drugs, such as opiates and nicotine—the common thread: increased dopamine levels.

All forms of learning and memory rely on synaptic plasticity, the ability of the brain to tweak the connections between neurons. These connections, or synapses, can be strengthened by a process known as long-term potentiation (LTP), which largely depends on the flow of calcium ions into and out of neurons. Morikawa's work suggests that repeated dopamine release somehow boosts the chances of LTP in the brain's reward pathways, although the molecular details are not yet clear.

Mice in booze camp
In the new study, performed on adolescent male mice, ethanol alcohol exposure seemed to enhance synaptic plasticity in the ventral tegmental area (VTA), a part of the brain that plays a critical role in the reward pathway. The VTA contains dopamine neurons whose axons extend to many other regions of the brain.

Researchers injected the mice with two grams of ethanol per kilogram of body weight three times daily for seven days. In humans this would be comparable to binge drinking, or blood alcohol levels roughly two to three times that of the U.S. legal driving limit of 0.08 percent, Morikawa says. Control mice underwent the same regimen but with injections of saline.

After one day of rest, mice were tested for "conditioned place preference," a common measure of reward-based conditioning. Mice were allowed to explore what resembles a long, narrow shoe box, consisting of two distinctive compartments, one with a mesh floor and white walls, the other with a grid floor and black walls. The mice initially showed no preference for either decor, splitting their time evenly between the two compartments. Each animal was then given a reward—a cocaine injection—in one of the compartments and subsequently confined to that compartment for 30 minutes.

After two cocaine injections the mice were again allowed to freely explore the compartments. The mice that had a week of saline injections increased their stay in the compartment where they had received cocaine by 7 percent. But the mice that had a week of ethanol injections—the "hard-drinkers"—lingered in their cocaine compartments much longer, increasing their time there by 14 percent. One week of heavy alcohol intake had increased the mice's ability to remember the context of a rewarding experience. The heightened potential for synaptic plasticity was temporary, lasting between a week and a month after ethanol injections stopped, according to the researchers.

They also observed these changes on a neuronal level by studying slices of VTA taken from sacrificed mice. By repeatedly stimulating neurons with electrodes, researchers were able to induce LTP, the strengthening of synapses. Neurons taken from ethanol-injected mice showed on average more than twice as much LTP than neurons from saline-injected mice.

Differences and details
A 2005 study of ethanol exposure in mice did not find enhancement of synaptic plasticity. But Anthony Riley, a psychologist at American University and co-author of the 2005 study, was not surprised by the new findings. The mice in the earlier study were given significantly less alcohol, were of a different breed, and were adult mice. "[Morikawa's team] trained and tested their animals during adolescence, a period associated with greater reinforcing effects of drugs. The parameters are dramatically different—that likely accounts for the difference in results," Riley says.

How does steady alcohol use encourage neurons to link up? The molecular mechanisms are complex and still somewhat speculative, Morikawa says, but it begins with the flood of dopamine caused by alcohol use. Autoreceptors on dopamine neurons sense the dopamine being released. Chronic activation of these autoreceptors revs up the activity of protein kinase A (PKA). PKA phosphorylates IP3 receptors located on cell membranes, inducing them to release intracellular stores of calcium ions. The flow of calcium ions eases communication between neurons, promoting LTP along the reward pathway.

Riley says this biochemical interpretation requires further confirmation, such as challenging part of the proposed mechanism to see if the effect is blocked: "That is needed for them to talk of a causal role in their effect."

From mice to men
Larry Zweifel, a pharmacologist at the University of Washington in Seattle who was not involved in Morikawa's or Riley's work, says that the new research shows that drug abuse can change the brain by "strengthening the capacity of neurons in the reward circuit to be strengthened, in effect setting up a positive feedback loop to drive persistent drug seeking."

If the thought of binge-drinking teenagers getting hooked on cocaine is stressing you out, Morikawa has more bad news. "People frequently drink to relieve daily stress, but that might actually provide an ideal setting to get hooked up to alcohol-associated stimuli and behavior very effectively," he says. When brain slices were bathed in a stress hormone, IP3-induced calcium signaling also increased. In fact, compared with ethanol, which enhances synaptic plasticity only after long-term use, "stress can do the same job more rapidly," Morikawa says.

It doesn't take a neuroscientist to know that avoiding temptations from a drug-addled past is a good idea, so why go to all the trouble of studying alcoholic mice? By understanding the basic mechanisms of drug addiction in animal models, "we can extrapolate these findings to develop selective therapies to reverse the pathophysiological changes associated with compulsive drug-seeking," Zweifel says.

Morikawa puts it in more straightforward terms: "The goal is not simple—we are talking about erasing certain memories without affecting others—but I believe it is an attainable goal," he says.

What if Osama bin laden was hooled up in India??

Those of you who are familiar with the political atmosphere in India will definitely find this article pretty interesting.

Ever since American Navy Seals killed Osama bin Laden in an operation inside Pakistan, idle talk has been going on here as to why India does not carry out similar daring missions. Banish the thought, friends. We would not even dream of such “unprecedented, unconstitutional and illegal” activity that militates against the principles of “ahinsa”.  Leave alone Pakistan, even if he were hiding here, we would have handled things strictly according to established democratic procedures. In all probability, the situation would have unfolded in the following fashion:  Policemen would have visited his house and after the customary grant of "kharcha-pani",  would have issued him a character certificate  that he was a bona fide Indian citizen named Osama Kumar with a yellow BPL (below poverty line) ration card.  He would have also armed himself with a stay order against any kind of forcible eviction. He would have also approached several minority organisations for support.  Some parties would have sent him feelers that if he joins their organisation, all his purported crimes would be forgiven and forgotten. Not only that, he would also be made head of the foreign cell of the party. Everybody is innocent till his guilt is proved in a court of law.  There may have also been a ban on causing any kind of damage to his house, it having been declared a protected monument.  The government would have taken at least 20 years to decide what impact a raid would have on Muslim votes. There would have been many seminars suggesting that instead of acting against him, the government should invite him to the negotiating table.  If at all action became unavoidable, there would have been a heated discussion to decide in which police station’s jurisdiction his house fell.  The satellite pictures of the locality where he was holed up would have been leaked out, not for what was found within his compound, but for the accidentally recorded salacious activities of couples living in the  neighbourhood. These would have been a rage on the MMS circuit.  Even if the government gathered the political courage to send a raiding party, Mayawati would have objected vehemently to the composition of the commando team if it did not have enough Dalit representation.  The moment the raiding helicopters became airborne, the news would have reached the dharna types, who would have started a relay fast and candlelight vigil atop his house protesting against such state-sponsored terrorism against an ailing, hapless person on flimsy grounds. Human rights organisations would have formed a human chain.  There would have been 50 OB vans of TV channels outside the house beaming minute-by-minute progress of the commando operation "exclusively".  The more enterprising ones would be even airing interviews of his family members, relatives, friends, neighbours and admirers shedding copious tears that he was totally innocent. The visuals of his philanthropic work would have been telecast repeatedly.  No question of his being shot. He would have been arrested – without being handcuffed, of course -- and would have gone to jail amidst lusty slogans such as "Obamaji aap sangharsh karo hum tumhare saath hain". Top lawyers would have come forward to defend him. Even if he were sentenced, he would have either been released in exchange for kidnapped relatives of some minister or would have been let off within a year or two due to good conduct in jail. He would have definitely won an election with a record margin and become a minister.  Publishing houses would have offered him billions for his autobiography. Bollywood too would have paid him astronomical sums to star in a multilingual film tentatively titled "Victim of Circumstances".  Oh Osama, if only you knew what a strategic blunder you made by going to Pakistan!

10 Best Series Finale

Our top 10 series finales list includes a couple of polarizing picks (you either loved or hated that Journey-blarin', onion-ring-noshing ending for a certain family of New Joisey-ans), a couple we're pretty sure you'll agree are gems and a number one pick that we'd argue is the most clever, most unexpected TV series finale ever.

WARNING: In case you're still catching up with some of these shows on DVD ... there be spoilers ahead.

10. 'The Wire'
Episode: '-30-'
Finale date: March 9, 2008
The big finish: Carcetti became governor, fabulist Templeton won a Pulitzer, Michael continued on his path of crime, promising student Dukie spiraled into a life of drugs and recovering addict Bubbles remained clean and was invited to dinner with his family. But the best moments of the finale came during the wake mock for soon-to-be former Baltimore detective Jimmy McNulty (Dominic West), one of the most complicated, hilarious, devoted and sometimes corrupt cop characters in TV history, from one of the most complicated, compelling and sadly underappreciated dramas in TV history.


9. 'Seinfeld'
Episode: 'The Finale'
Finale date: May 14, 1998
The big finish: Sure, we know, it's a polarizing episode, and some fans thought it was an ending unworthy of such a classic show. But we say it was a perfectly appropriate way to go out, as the "show about nothing" saw the four famous friends head off to the hoosegow precisely because they did nothing. Failure to do anything while they witnessed a man being robbed got Jerry, Elaine, George and Kramer slapped with jail time after being convicted of criminal indifference, but it also provided the perfect opportunity to bring back a sea of the show's famous guest characters, from the Soup Nazi to nutty David Puddy and every Babu, Low Talker and Poppy in between. Not to mention the judge: Arthur Vandelay.


8. 'Arrested Development'
Episode: 'Development Arrested'
Finale date: Feb. 10, 2006
The big finish: 'AD' devotees are still bummed the show lasted just three seasons, but at least we got a proper series finale and the show ended on a high note. Bluth family martyr Michael (Jason Bateman) finally decided to put himself and his son, George Michael (Michael Cera). ahead of his greedy, self-obsessed relatives, so he scooted off to Cabo and left his fam to deal with their self-created messes. In Cabo, Michael awoke to find his father had followed him. And, in one of the show's best meta moments, underage studio exec Maeby, Michael's niece, pitched a story about her family to a big Hollywood producer: Ron Howard, an 'AD' producer and the man behind the show's voiceovers, who cheekily tells her the Bluths would inspire a better movie than TV show. PS -- We're still waiting on that movie, Opie.


7. 'The Mary Tyler Moore Show'
Episode: 'The Last Show'
Finale date: March 19, 1977
The big finish: When new owners took over WJM and wanted to boost the station's ratings, they fired everyone competent -- including Mary (Mary Tyler Moore), Mr. Grant (Ed Asner), Murray (Gavin MacLeod) and Sue Ann (Betty White) -- and kept on Ted Baxter (Ted Knight), one of the main reasons the evening news was so low-rated. Most of the staff took the news in stride -- Mr. Grant flew in Mary's old pals Rhoda (Valerie Harper) and Phyllis (Cloris Leachman) to cheer her up -- but in what has become one of the most memorable scenes in TV land, the pals all bid each other farewell in the newsroom with a teary group hug that included a group shuffle to the tissue box.


6. 'Cheers'
Episode: 'One for the Road'
Finale date: May 20, 1993
The big finish: The 'Cheers' finale showed us once and for all whether or not sitcom super-couple Sam and Diane belonged together; they did not. Sam, as pal Norm pointed out, would only be at home with his one true love, the place where everybody knows your name.


5. 'M*A*S*H'
Episode: 'Goodbye, Farewell and Amen'
Finale date: Feb. 28, 1983
The big finish: The only thing more shocking than Klinger's decision to remain in Korea after the war? The real reason behind Hawkeye's (Alan Alda) meltdown in the iconic show's series finale, one of the most-watched TV episodes ever. As the clip below shows, Alda (who earned an Emmy nomination for directing the series finale) turned Hawkeye's usual flipness into a full-on breakdown as his psychiatrist forced him to remember the crushing death of an infant, a death he blamed on himself. Fortunately, the episode ended on a lighter, yet still emotionally powerful, note, with Hawkeye discovering the special "Goodbye" his BFF Hunnicutt (Mike Farrell) had left for him ... spelled out in rocks.


4. 'The Shield'
Episode: 'Family Meeting'
Finale date: Nov. 25, 2008
The big finish: Oh, Shane. Mr. Vendrell and his family's demise is still so shocking and heartbreaking that it's made better only by the fact that Shane's portrayer, the incredible Walton Goggins, is now making his case for an Emmy on another great FX drama, 'Justified.' The Vendrell family was but a sample of those whose lives were ruined by the wily, completely corrupt Vic Mackey (Michael Chiklis), who, in the end, was on the receiving end of the most satisfying bit of karma in TV history: a desk job.


3. 'The Fugitive'
Episode: 'The Judgment'
Finale date: Aug. 29, 1967
The big finish: For four seasons, Dr. Richard Kimble (David Janssen) had been on the lam, trying to clear his own name in the murder of his wife by tracking down the real culprit, the One-Armed Man. Every episode of the series was a gem, full of action and suspense, and it all paid off in the series ender, as Kimble finally cornered OAM at an amusement park, cleared his good name and reputation and even shook hands with Philip Gerard, the lawman who had been hot on Kimble's trail throughout the show.


2. 'The Sopranos'
Episode: 'Made in America'
Finale date: June 10, 2007
The big finish: Sure, everyone was yelling at their TV screens when it aired, and it was only with a bit of perspective that we came to appreciate the brilliance of this ending: Even when half of his friends had been whacked and he was potentially facing some serious jail time, life went on for Tony Soprano. Or, maybe it was about how he never saw the end of his life coming. Again, that's the brilliance of the hotly-debated, ambiguous ending, which series creator David Chase has only commented on vaguely in the years since the finale aired. We're choosing to believe Tony survived, though this incredibly comprehensive counter-argument could sway us to the other side.

P.S.: We've been to Holsten's and have sampled those onion rings ... killer.



1. 'Newhart'
Episode: 'The Last Newhart'
Finale date: May 21, 1990
The big finish: It was all a dream! But not in that Bobby Ewing–in-the-shower kinda way (actually, a lot like that, except hilarious ... intentionally so), as Chicago psychiatrist Bob Hartley -- the character Bob Newhart played in his otherclassic sitcom, 'The Bob Newhart Show' -- woke up in bed with his wife Emily (Suzanne Pleshette), meaning the entire series of 'Newhart,' in which the titular star played Vermont innkeeper/do-it-yourself book author Dick Loudon, was all a dream. Yes, even Larry, his brother Darryl, and his other brother Darryl.