Implantation, Hcg Rise, and Sex!

The emotional roller coaster keeps going. Assuming the trigger worked as it should, today is 1 DPO. I went from decently optimistic the day after trigger to more pessimistic today. No real reason for that. I'm usually really fortunate in that I have very few side effects from the stim meds. In fact, my estrogen and progesterone are so low when not stimming that I typically have night sweats, and those go away during stims, so it's a nice change! This time I've noticed much more bloating, especially after trigger. I can't tell with any certainty if my ovaries are sore of if it's just my colon, but on the whole, this cycle has been more symptomatic than past. Bummer.

Because I enjoy thinking about what might be happening, fertility wise, here are a few articles on the topic of 'when does implantation happen' and 'when is hcg detectable'? I tried to focus on results from top-tier publications.


This 1999 study, published in the NEJM, used daily hormone measurements to track ovulation and identify implantation based upon the first day of detectable hcg. Then they compared implantation day with outcomes. They found that in the majority of pregnancies (84%), implantation occurred on days 8, 9, or 10. The percentage of pregnancies ending in early loss was highly correlated with implantation day: 82% of pregnancies with implantation after day 11 ended in early losses, compared to 13% of pregnancies that implanted by the ninth day. Perhaps this is why my clinic has me test at 14 days post trigger/12 days post ovulation? That seems low compared to many other places, but makes sense in light of this.

N Engl J Med. 1999 Jun 10;340(23):1796-9.

METHODS:
We collected daily urine samples for up to six months from 221 women attempting to conceive after ceasing to use contraception. Ovulation was identified on the basis of the ratio of urinary estrogen metabolites to progesterone metabolites, which changes rapidly with luteinization of the ovarian follicle. The time of implantation was defined by the appearance of chorionic gonadotropin in maternal urine.

RESULTS:
There were 199 conceptions, for 95 percent of which (189) we had sufficient data for analysis. Of these 189 pregnancies, 141 (75 percent) lasted at least six weeks past the last menstrual period, and the remaining 48 pregnancies (25 percent) ended in early loss. Among the pregnancies that lasted six weeks or more, the first appearance of chorionic gonadotropin occurred 6 to 12 days after ovulation; 118 women (84 percent) had implantation on day 8, 9, or 10. The risk of early pregnancy loss increased with later implantation (P<0.001). Among the 102 conceptuses that implanted by the ninth day, 13 percent ended in early loss. This proportion rose to 26 percent with implantation on day 10, to 52 percent on day 11, and to 82 percent after day 11.


Another situation I've always wondered: I read that hcg is supposed to double roughly every 48 hours during the early weeks. But given that it must start from 0, how do you get from 0 to detectable in only a few days? This study looked at hcg patterns, and found a 3-fold rise between the day hcg is first detected and the next day. The rate of increase later dropped to 1.6x by days 6 and 7 after detection (roughly 4 weeks pregnant, and the time of the first beta).

Hum Reprod. 2008 Feb;23(2):271-7. Epub 2007 Dec 14.
METHODS:
We measured daily hCG concentrations in first-morning urine for 142 clinical pregnancies from women with no known fertility problems. Mixed-effects regression models were used to estimate the hCG trajectory and its variability in relation to pregnancy outcomes.

RESULTS:
hCG rose 3-fold between the day of detection and the next day (95% CI = 2.7-3.4). The relative rate of rise decreased thereafter, reaching 1.6-fold (95% CI = 1.5-1.8) between days 6 and 7. HCG levels followed a log-quadratic trajectory, and the patterns of rise were unrelated to number of fetuses, risk of spontaneous abortion or sex of the baby. Later implantations (after 10 luteal days) produced slower rates of increase.

CONCLUSIONS:
Although mean hCG follows a log-quadratic trajectory during the first week of detectability, there is high variability across pregnancies. Later implantation may reflect characteristics of the uterus or conceptus that slow hCG production.


Finally, to the question of when to have timed intercourse, here's another NJEM-published study looking at fertile people. There are a number of these studies, but I like this one because it used hormones to track ovulation, rather than relying on temperature records, which are more unreliable. The study found the highest probability of conception when TI occurred the day before ovulation. Another paper, reviewing many on the subject, noted that studies where ovulation is determined by hormones typically find the day before ovulation to have the highest probability of conception, while studies where ovulation is determined by basal temperature/charting typically find the day of ovulation to have the highest probability. I trust hormones more than temperatures, so I'll assume day before is optimal based on what we know.

N Engl J Med. 1995 Dec 7;333(23):1517-21.
METHODS:
We recruited 221 healthy women who were planning to become pregnant. At the same time the women stopped using birth-control methods, they began collecting daily urine specimens and keeping daily records of whether they had sexual intercourse. We measured estrogen and progesterone metabolites in urine to estimate the day of ovulation.

RESULTS:
In a total of 625 menstrual cycles for which the dates of ovulation could be estimated, 192 pregnancies were initiated, as indicated by increases in the urinary concentration of human chorionic gonadotropin around the expected time of implantation. Two thirds (n = 129) ended in live births. Conception occurred only when intercourse took place during a six-day period that ended on the estimated day of ovulation. The probability of conception ranged from 0.10 when intercourse occurred five days before ovulation to 0.33 when it occurred on the day of ovulation itself. There was no evident relation between the age of sperm and the viability of the conceptus, although only 6 percent of the pregnancies could be firmly attributed to sperm that were three or more days old. Cycles producing male and female babies had similar patterns of intercourse in relation to ovulation.